Nutraceuticals are products derived or isolated from natural or food sources that provide a benefit in the health of individuals consuming them or that prevent or delay the onset of certain disorders or diseases, in addition to the basic nutritional value thereof. That is the reason why the consumers are increasingly demanding this kind of products and why research and development in the field of nutraceuticals is becoming more and more important in the food, pharmaceutical and veterinary industry.
The research in the field of nutraceutical and functional foods is directed into different lines such as the identification and development of microorganisms that may confer a healthy benefit on the host, commonly known as probiotics, or the isolation of natural compounds or substances present in natural or food products which exert a beneficial effect on the health of the person consuming them.
One of the natural compounds that have proven to have beneficial effects in the health is D-fagomine.
D-fagomine (2R, 3R, 4R)-2-hydroxymethylpiperidine-3,4-diol, is a natural iminocyclitol, a polyhydroxylated piperidine which was first isolated from buckwheat seeds of Faqopyrum esculentum Moench and later from other plant sources such as mulberry (Morus alba, Moraceae), gogi (Lyceum chinense), Castanospermum australe, Xhanthocercis zambesiaca leaves and Morus bombycis leaves. The D-fagomine (2R, 3R, 4R)-2-hydroxymethylpiperidine-3,4-diol is shows in the formula below.

Among other functions, D-fagomine has been taught to decrease postprandrial blood glucose level without stimulating insulin secretion (Gomez L. et al. Br. J. Nutr. 2012 June; 107(12):1739-46). As such D-fagomine has been proposed as a useful dietary ingredient or functional food component to reduce the health risks associated with an excessive intake of fast-digestible carbohydrates.
WO2011117362 discloses the capacity of D-fagomine of inhibiting bacterial adherence to mucosal surface. Since bacterial adherence to mucosa is an important prerequisite for colonization and infection, D-fagomine is considered a valuable agent for the prevention and/or coadjuvant treatment of bacterial infection. In addition, this document discloses that D-fagomine is also useful for preventing micloflora imbalance caused by enteric, oral or respiratory pathogenic bacteria. This effect is due to the fact D-fagomine adheres to harmful bacteria such as certain strains of the genus Escherichia, Salmonella or Streptococcus but not to healthy ones such as Lactobacili or Bifidobacteria. In these sense, healthy bacteria are more tendent to implantation in the mucosa than pathogen ones.
The research done (Gomez L, et al), also confirms that D-fagomine do not show antimicrobial activity, that means that, although there is an specific effect on the adhesion of some bacteria the viability of these bacteria are not affected by the presence of D-fagomine. Other prior art document also refer to the biological function of D-fagomine and its N-alkylated derivatives (Castillo J. A. et al. “Fructose-6-phosphate alolase in organic synthesis: preparation of D-fagomine; N-alkylated derivatives, and preliminary biological assays” Organic letter 2006 Vol. 8 (26): 6067-6070). Castillo J. A et al describes that D-fagomine and N-alkylated derivatives C4, C6, C8, C9 and Ph-CH2 do not show antimicrobial activity.
Now, the authors of the present invention have discovered a new biological function of D-fagomine. In particular, they have found that D-fagomine has the capacity to trigger mechanisms of innate immune response at the level of the mucosa. The improvement of the mechanisms of innate immune response helps individuals to prevent and reduce infections from potential pathogens microorganisms near the mucosa. Additionally, this improvement of the natural mechanisms of the innate immune system protection at the mucosa level avoids the undesirable overactivation of the humoral immune response which is the second relevant defense against microorganisms. Said humoral immune response which is carried out by the adaptative immune system is generally more potent and systemic. Its overactivation contributes to the onset of chronical subclinical inflammation situations.
The improvement of innate immune response is relevant to maintain under control not only bacteria but also to virus and other parasites.
Microorganisms are considered to maintain the correct activity level in our innate immune system. It has been proposed that an unnatural development of the immune system and particularly of the innate immune system results in an increased susceptibility to autoimmune diseases. Celiac, Crohn's disease and ulcerative colitis for example, have been related to this abnormal response. The absence or malfunction of innate immune response contributes to the overactivation the humoral immune response that may result in uncontrolled damaging autoimmune responses. Up to 100 types of autoimmune disease including asthma, multiple sclerosis, lupus, psoriatic and reumathoid arthritis, and diabetes have been identified.
Also chronic subclinical inflammation derived for an altered interaction between the gut microbiota and the host is considered to potentiate the humoral inflammatory response, and is deemed to be the cause governing the rate of progression of the metabolic syndrome and other diseases such as obesity, hypertension, type II diabetes, fatty liver, Alzheimer or cancer (e.g. breast, colon).
It is then of great interest to find new ways of naturally reinforcing the innate immune response at the local mucosal level by, at the same time, decreasing the risk of undesirable potent humoral immune response.
The innate immune system represents the first line of defense of the organism and comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner. This means that the cells of the innate system recognize and respond to pathogens in a generic way, but unlike the adaptive immune system, it does not confer long-lasting or protective immunity to the host. Innate immune systems provide immediate defense against infection. It is formed by different types of cells such as Mast cells, phagocytes (macrophages, neutrophils and dendritic cells), basophils and eosinophils and Natural Killer cells (NK cells) as well as by biochemical mechanism such as the complement system.
The major functions of the vertebrate innate immune system include:    a) Recruiting immune cells to sites of infection, through the production of chemical factors, including specialized chemical mediators, called cytokines.    b) Activation of the complement cascade to identify bacteria, activate cells and to promote clearance of dead cells or antibody complexes.    c) The identification and removal of foreign substances present in organs, tissues, the blood and lymph, by specialised white blood cells.    d) Activation of the adaptive immune system through a process known as antigen presentation.    e) Acting as a physical and chemical barrier to infectious agents.
The present inventions is based in the demonstration made by inventors that the cells of the innate immune system present in the mucosa release cytokines such as TNF-α in the presence of D-fagomine.
The enhancement of the innate immune response in the mucosa represents a natural mechanism of protection against pathogens since it maintains a natural defense that avoids triggering the more potent, aggressive and systemic response of the adaptive immune system against pathogens capable of avoiding or hiding the natural defenses of the mucosa. The presence of an “activated” innate immune system avoids the triggering of mechanisms of acute response against certain pathogen bacteria so adapted to the medium that with the pass of time are responsible of chronical subclinical inflammatory processes.